Embryotoxicity of carbamazepine in rat postimplantation embryo culture after in vitro exposure via three different routes. 1998

A H Piersma, and A Verhoef, and A Opperhuizen, and R Klaassen, and J van Eijkeren, and M Olling
Health Effects Research Laboratory, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

Postimplantation rat embryo culture is used widely for studies of embryotoxic effects on the isolated embryo after in vitro exposure to xenobiotic compounds. In this study, the relevance of three routes of exposure of the embryo in vitro was evaluated using the embryotoxic anticonvulsant carbamazepine. Embryotoxic effects were assessed, and analyses in conceptus tissues were done to reveal uptake and metabolism of the compound. Exposure via the culture medium resulted in neural tube defects and general retardation of growth and development. After injections into the amniotic or exocoelomic space, local membrane adhesions were found. Intra-amniotic exposure caused adhesions of the amniotic membrane with the embryonic neural plate, resulting in trapping of the membrane in the closing neural tube, as well as in open neural tube defects occurring in various areas of the neural tube. Only after exposure via the culture medium were amounts of carbamazepine detectable in the embryonic tissue, correlating with the systemic effects found. It is concluded that uptake from the culture medium via the yolk sac circulation is the relevant exposure route to be used for embryotoxicity effect assessment.

UI MeSH Term Description Entries
D007267 Injections Introduction of substances into the body using a needle and syringe. Injectables,Injectable,Injection
D009436 Neural Tube Defects Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy generally occurring between days 18-29 of gestation. Ectodermal and mesodermal malformations (mainly involving the skull and vertebrae) may occur as a result of defects of neural tube closure. (From Joynt, Clinical Neurology, 1992, Ch55, pp31-41) Craniorachischisis,Developmental Defects, Neural Tube,Diastematomyelia,Exencephaly,Neurenteric Cyst,Spinal Cord Myelodysplasia,Tethered Cord Syndrome,Acrania,Developmental Neural Tube Defects,Iniencephaly,Neural Tube Developmental Defects,Neuroenteric Cyst,Occult Spinal Dysraphism,Occult Spinal Dysraphism Sequence,Tethered Spinal Cord Syndrome,Acranias,Craniorachischises,Cyst, Neurenteric,Cyst, Neuroenteric,Cysts, Neurenteric,Cysts, Neuroenteric,Defect, Neural Tube,Defects, Neural Tube,Diastematomyelias,Dysraphism, Occult Spinal,Dysraphisms, Occult Spinal,Exencephalies,Iniencephalies,Myelodysplasia, Spinal Cord,Myelodysplasias, Spinal Cord,Neural Tube Defect,Neurenteric Cysts,Neuroenteric Cysts,Occult Spinal Dysraphisms,Spinal Cord Myelodysplasias,Spinal Dysraphism, Occult,Spinal Dysraphisms, Occult,Tethered Cord Syndromes
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D002220 Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties. Amizepine,Carbamazepine Acetate,Carbamazepine Anhydrous,Carbamazepine Dihydrate,Carbamazepine Hydrochloride,Carbamazepine L-Tartrate (4:1),Carbamazepine Phosphate,Carbamazepine Sulfate (2:1),Carbazepin,Epitol,Finlepsin,Neurotol,Tegretol
D003470 Culture Media Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN. Media, Culture
D004333 Drug Administration Routes The various ways of administering a drug or other chemical to a site in a patient or animal from where the chemical is absorbed into the blood and delivered to the target tissue. Administration Routes, Drug,Administration Route, Drug,Drug Administration Route,Route, Drug Administration,Routes, Drug Administration
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D005260 Female Females
D000267 Tissue Adhesions Pathological processes consisting of the union of the opposing surfaces of a wound. Adhesions, Tissue,Surgery-Induced Tissue Adhesions,Surgical Adhesions,Adhesion, Surgery-Induced Tissue,Adhesion, Surgical,Adhesion, Tissue,Adhesions, Surgery-Induced Tissue,Adhesions, Surgical,Surgery Induced Tissue Adhesions,Surgery-Induced Tissue Adhesion,Surgical Adhesion,Tissue Adhesion,Tissue Adhesion, Surgery-Induced,Tissue Adhesions, Surgery-Induced
D000650 Amnion The innermost membranous sac that surrounds and protects the developing embryo which is bathed in the AMNIOTIC FLUID. Amnion cells are secretory EPITHELIAL CELLS and contribute to the amniotic fluid. Amniotic Membrane,Amnions,Amniotic Membranes,Membrane, Amniotic,Membranes, Amniotic

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